Enantioselective resolution of chiral aromatic acids by biphasic recognition chiral extraction

This paper reports a new chiral separation technology—biphasic recognition chiral extraction for the separation of aromatic acid enantiomers such as α-cyclohexyl-mandelic acid (CHMA) and naproxen (NAP). The biphasic recognition chiral extraction system was established by adding hydrophobic d(l)-isobutyl tartrate in 1,2-dichloroethane organic phase and hydrophilic β-cyclodextrin (β-CD) derivative in aqueous phase, which preferentially recognize the (R)-enantiomer and (S)-enantiomer, respectively. These studies involve an enantioselective extraction in a biphasic system, where aromatic acid enantiomers form complexes with the β-cyclodextrin derivative in the aqueous phase and d(l)-isobutyl tartrate in the organic phase, respectively. Factors affecting the extraction mechanism are analyzed, namely the influence of the concentrations of the extractants and aromatic acid enantiomers, the types of the extractants, pH, and temperature. The experimental results show that the biphasic recognition chiral extraction is of much stronger chiral separation ability than the monophasic recognition chiral extraction, which utilizes the cooperations of the forces of the tartrate and the β-CD derivative. Hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (ME-β-CD) have stronger recognition abilities for the (S)-aromatic acid enantiomers than those for (R)-aromatic acid enantiomers, among which HP-β-CD has the strongest ability. d-Isobutyl tartrate preferentially recognizes (R)-CHMA and (S)-NAP, while l-isobutyl tartrate preferentially recognizes (S)-CHMA and (R)-NAP. The maximum enantioselectivities of CHMA and NAP are 2.49 and 1.65, under conditions at which the pH values of the aqueous phases are 2.7 and 2.5, at the ratio of 2:1 of [isobutyl tartrate] to [HP-β-CD].     

Efficient soluble polymer-supported tartrate/Ti catalyst for asymmetric oxidation of prochiral sulfides

A group of soluble polymer-supported chiral tartrate ligands was prepared by liquid-phase synthesis with ligand diversity strategy. Moderate to excellent chemical yields and enantiomeric excesses were obtained by using soluble polymer-supported tartrate ester in asymmetric oxidation of prochiral sulfides using Ti(O-i-Pr)₄/cumyl hydroperoxide, and the workup was greatly simplified. The influence of substituent in chiral tartrate ligands on the enantioselectivities of the reaction was disclosed.     

Development and Validation of a New LC Method for Analysis of Brimonidine Tartrate and Related Compounds

A novel liquid chromatographic method for analysis three potential impurities in brimonidine tartrate drug substance has been developed and validated. Efficient chromatographic separation was achieved on a C₈ column (250 mm × 4.6 mm, 5-μm particles) with a simple mobile-phase gradient at a flow rate of 1.0 mL min^?1. Quantification was achieved by use of ultraviolet detection at 248 nm. Resolution between brimonidine tartrate and its three potential impurities was greater than 3.0. Regression analysis showed the r value (correlation coefficient) was >0.999 for brimonidine and its three impurities. The method was capable of detecting all three impurities of brimonidine tartrate at levels below 0.07 μg in a test concentration of brimonidine tartrate of 1.0 mg mL^?1 and for an injection volume of 10 μL. A solution of brimonidine tartrate in acetonitrile–water 2:8 (v/v) was stable for 48 h. The drug was subjected to stress conditions as prescribed by the ICH. Degradation was found to occur slightly under oxidative stress conditions but the drug was stable to aqueous, acidic, and basic hydrolysis, and photolytic and thermal stress. The assay of the stressed samples was calculated relative to a qualified reference standard and the mass balance was found close to 99.8%. The method was validated for linearity, accuracy, precision, and robustness.     

Sol–gel synthesis,crystal structure,surface morphology,and optical properties of Eu2O3-doped La2Mo3O12 ceramic

In this paper, we report the synthesis of the La–Mo–O tartrate gel precursors with the initial composition for La₂Mo₃O₁₂ ceramic prepared from different starting materials by an aqueous sol–gel synthesis route using tartaric acid as a complexing agent. Moreover, the La–Mo–O carbonate–tartrate and nitrate–tartrate gel precursors doped with x % of Eu₂O₃ (x = 0.5, 1.0, 2.0, 4.0, and 8.0) by aqueous sol–gel synthesis method were also prepared. The thermal decomposition of both the La–Mo–O carbonate–tartrate and nitrate–tartrate gels, which is the critical stage of this preparation technique, is investigated in detail. X-ray diffraction, scanning electron microscopy, and ultraviolet–visible spectroscopy were used for the determination of crystal structure, surface morphology, and optical properties of the La–Mo–O:xEu₂O₃ samples annealed at 400, 500, 600, 700, 800, 900, and 1,000 °C temperatures, respectively. The obtained results show that the thermal decomposition of the La–Mo–O tartrate gel precursors has occurred in a separate manner. The differences that came up during the thermal treatment of La–Mo–O tartrate gels have related only with the initial composition that determined the different crystallization ways of final compounds. Besides, the dopant concentration mainly influences the size of obtained particles and agglomeration of synthesized final materials. The initial composition of the La–Mo–O gel precursors has significant influence on the formation of final crystal phases at relatively lower temperatures than was expected according to the TG–DTA measurements. Finally, the optical properties of La–Mo–O tartrate gel precursors annealed at 500 °C depend on the nature of the initial compounds, which were used during the aqueous sol–gel process.     

Properties of the ammonium tartrate/EPR dosimeter

The EPR response of γ-irradiated ammonium tartrate on the absorbed dose of γ-rays up to 22 kGy as well as the changes in the shape of the EPR spectrum upon applied modulation amplitude and microwave power are reported. Also the possibility to use ammonium tartrate together with Mn²⁺ magnetically diluted in MgO as an internal reference material is evaluated. The influence of the microwave power and the modulation amplitude on their dose response is investigated. The results show that the radiation-induced EPR spectrum of ammonium tartrate, obtained at a low microwave power is complex consisting several patterns and is more easily saturated than the Mn²⁺ EPR spectrum. In this case the following settings of the EPR parameters are recommended: H_mod⩽0.05 mT and 10⩽P_MW⩽13 mW. Using these parameters the dosimeters can be considered for use in intercomparisons.     

Final product analysis in the e-beam and gamma radiolysis of aqueous solutions of metoprolol tartrate

The radiostability of metoprolol tartrate aqueous solutions and the influence of the absorbed dose (0–50 kGy), dose rate (e-beam (EB) vs. gamma (γ)) and radioprotectors (pharmaceutical excipients) are investigated by HPLC-UV analyses and through computer simulations. The use of radioprotecting excipients is more promising than an increase in the dose rate to lower the degradation of metoprolol tartrate aqueous solutions for applications such as radiosterilization. The decontamination of metoprolol tartrate from waste waters by EB processing appears highly feasible.     

Enantioselective fluorescent sensor for dibenzoyl tartrate anion based on chiral binaphthyl derivatives bearing an amino acid unit

The fluorescent photoinduced electron transfer (PET) chemosensors 1–3 based on (S)-1,1′-bi-2-naphthol were designed for their recognition of dibenzoyl tartrate anions. The binding properties for hydroxy acid anions were examined by the fluorescence and ¹H NMR spectra. The results indicated that receptor 1 exhibit excellent enantioselectivity toward the enantiomers of dibenzoyl tartrate anion.     

Determination and correlation of solubility of tylosin tartrate in alcohol mixtures

Data on (solid + liquid) equilibrium of tylosin tartrate in {methanol + (ethanol, 1-propanol or 2-propanol)} solvents will provide essential support for industrial design and further theoretical studies. In this study, the solubility of tylosin tartrate in alcohol mixtures was measured over temperature range from (278.15 to 323.15) K under atmospheric pressure by a gravimetric method. From the experimental results, the solubility of tylosin tartrate in selected solvents noted above was found to increase with increasing temperature and mass fraction of methanol. The solubility data were correlated with the modified Apelblat equation, the λh equation and van’t Hoff equation. The results showed that the three equations agreed well with the experimental values, and that the modified Apelblat equation was more accurate than the λh equation and van’t Hoff equation. Further, the standard enthalpy, standard entropy and standard Gibbs free energy of solution of tylosin tartrate in mixed solvents were calculated according to solubility results, model parameters with modified Apelblat equation and van’t Hoff equation.     

Investigation of dialkyl tartrate molecular recognition in cluster ions by Fourier transform mass spectrometry: a comparison of chirality effects in gas and liquid phases

Electrospray ionization of equimolar solutions of S-dimethyl tartrate and R-d6-dimethyl tartrate in methanol/water/acetic acid/salt solutions was utilized to investigate molecular recognition processes in solution. Pronounced chirality effects previously reported for formation of the protonated dimer by ion molecule reactions in the gas phase are quantitatively reproduced in experiments which sample solution phase protonated dimers. Ab initio quantum calculations demonstrate that hydrogen bonds in the protonated cluster are responsible for molecular recognition and that Li⁺ bound clusters, which do not exhibit chiral recognition, are primarily bound by electrostatic forces. In contrast with gas phase studies of alkali and ammonium ion core dimers of dimethyl tartrate—which show no chirality effects—ions electrosprayed from solutions containing trace amounts of these ions show pronounced chirality. With increasing salt concentration the apparent chirality effect disappears and a statistical distribution identical to that found for the gas phase is obtained. These observations are rationalized by a kinetic model that considers the displacement of protons by alkali ions in the final stages of desolvation of microdroplets formed in the electrospray process.     

Half-wave potentials of metal ions in organic hydroxyacid supporting electrolytes.II

Information is presented on the half-wave potentials, reversibilities, wave shapes, and probable electrode reaction products for the polarographic waves of most of the common heavy metal ions in 0.1 F ammonium citrate at pH 6 and in 0.1 F ammonium citrate, malonate, oxalate, and tartrate containing 0.1 F ammonia.     

Solid-state study of hydrazonium tartrate and deuterated hydrazonium tartrate enantiomers

A study of the crystallographic, optical, and thermochemical properties of hydrazonium tartrate and deuterated hydrazonium tartrate enantiomers is described. Crystals of the enantiomers are orthorhombic with a tetramolecular cell. The space group is P2₁2₁2₁ with the lattice parameters a₀ = 7.640 ± 0.002 Å, b₀ = 13.441 ± 0.003 Å, and c₀ = 7.029 ± 0.002 Å. No change in lattice parameters is observed on deuteration. Optical second harmonic powder analysis shows the crystals to be phase matchable at 1.06 μm with d^2ω = 11 d^2ωα-SiO₂. The optical nonlinearity being unaffected by deuterium substitution is attributed to the nonlinear electronic polarizability of the hydrogen bonds. Crystals are transparent from 239 nm to 1.61 μm. Deuteration shifts the long wavelength cutoff to 2.07 μm, without affecting the band edge.     

Determination of semimicro amounts of tellurium by electrodeposition

Electrodeposition of tellurium in micro or semimicro amounts can be achieved using copper or copper-plated platinum cathodes. Best results are obtained from electrolytic baths of approximately 2 M sulfuric acid, 0.4 M ammonium sulfate, 0.1 M sodium tartrate and 0.06 M sodium nitrate. Electrodeposition of tellurium can be carried out with an accuracy better than 1% at the 90% confidence level.     

An optimised and recoverable tartrate surrogate for sharpless asymmetric epoxidations

The tetrahydroxy diester 7d (R = ⁱPr) is almost as effective as diisopropyl tartrate in SAE reactions of (E)-allylic alcohols and can be recovered and re-used following a relatively simple work-up procedure.     

Catalytic asymmetric S-oxidation of N-benzoyl-1,5-benzothiazepines

An efficient catalytic asymmetric oxidation reaction of N-benzoyl-1,5-benzothiazepines using a chiral titanium complex formed in situ from Ti(O-iPr)₄, (R, R)-diethyl tartrate was developed. This reaction is helpful for the synthesis of the active form of (E, aS, 1S)-sulfoxide of N-benzoyl-1,5-benzothiazepines which should be recognized by vasopressin receptors. Furthermore, a prospective dynamic kinetic resolution utilizing this system was achieved.     

Conductivity studies on aqueous solutions of stereoisomers of tartaric acids and tartrates. Part I. Alkali metal and ammonium tartrates

Conductivity measurements on aqueous solutions of disodium tartrate, dipotassium tartrate, sodium potassium tartrate, and diammonium tartrate were performed in the temperature range 5 to 35°C. The equivalent limiting conductivity of tartrate anion, λ^∞(l/2 Tar^2-) is evaluated.     

Raman optical activity of tartaric acid and related molecules

The Raman optical activity spectra of (2R, 3R) (+)- and (2S,3S) (?)-tartaric acid, (2R, 3R) (+)-dimethyl tartrate, (2R,3R) (?)-2,3-butanediol and (2S, 3S) (+)-dibenzoyl tartaric acid are presented. A large couplet at about 500cm^?1 in the first three molecules, which probably originates in deformations of a chiral structural unit, might serve as an indicator of conformation and absolute configuration.     

Asymmetric oxidation of 3-alkyl-1,2-cyclopentanediones. Part 3: Oxidative ring cleavage of 3-hydroxyethyl-1,2-cyclopentanediones: synthesis of α-hydroxy-γ-lactone acids and spiro-γ-dilactones

A Ti(OiPr)₄/diethyl tartrate/tBuOOH complex oxidizes 3-hydroxyethyl-1,2-cyclopentanediones, resulting in hydroxylated/ring cleavage products—lactone acids of high enantioselectivity (up to 95% ee) with good yields (up to 75%). These compounds are converted into chiral spiro-γ-dilactones in good yield.     

Synthesis,crystal structure,and properties of a new lanthanide tartrate coordination polymer

A new coordination polymer of terbium tartrate [Tb(H₂O)₃(C₄H₅O₆)(C₄H₄O₆)] has been synthesized and crystallizes in the polar space group P4₁ with cell constants a = 6.0415(9), b = 6.0415(9), c = 36.516(7) Å, V = 1332.8(4) ų, Z = 4. The terbium(III) ion of title complex is nine-coordinate through oxygen donors. Four different coordination modes of tartrate occur. This Tb(III) complex exhibits a characteristic luminescence in the visible region upon excitation at 353 nm. The temperature-dependent magnetic properties of the Tb(III) complex were investigated in the temperature range of 2–300 K. Title compound exhibits significant ferroelectric properties at room temperature (remnant polarization 2P _r = 0.160 μC cm^?2, coercive field 2E _c = 44.5 kV cm^?1, saturation of the spontaneous polarization P _s = 0.176 μC cm^?2).     

Preparation of novel N-sulfonylated (S,S)-2,3-diaminosuccinate-type chiral auxiliaries and application to an asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides to allyl alcohol

Novel N-sulfonylated (S,S)-2,3-diaminosuccinate-type chiral auxiliaries, which have the tartaric acid-like framework with a sulfonamide group instead of a hydroxyl group, were synthesized from l-aspartic acid. The synthesized (S,S)-2,3-diaminosuccinate derivatives were applied to an asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides to allyl alcohol to afford the corresponding optically active 2-isoxazolines, with the enantioselectivities of up to 73% ee. The enantiofacial differentiation was intriguingly opposite to that by using diisopropyl tartrate as a chiral auxiliary.     

An improved heterogeneous asymmetric epoxidation of homoallylic alcohols using polymer-supported Ti(IV) catalysts

Heterogeneous asymmetric epoxidation of homoallylic alcohols has been achieved using polymer-supported Ti(IV) catalysts with tert-butyl hydroperoxide as oxidant. The enantioselectivities and chemical yields obtained are significantly higher (ee values up to 80%) than with monomeric tartrate ligands.